The proposed research consists of two parts - (a) the development of reasonable self- consistent scales and reference standards for the activities of the common cations and anions in biological and saline media, and the application of these results in refining procedures for the determination of ionic activities with ion-selective electrodes in media of biological interest, and (b) the investigation of ionic equilibria under the "real conditions of finite ionic strength (as opposed to infinite dilution) encountered in saline media of clinical importance. In part 1, formulas for the separation of mean activities into their ionic components will be derived primarily from Pitzer's ion-interaction theory. When necessary, mean activity coefficients will be measured by emf method. In part 2, electromotive-force measurement techniques will also be used to determine dissociation constants and associated thermodynamic data for ionic processes in saline systems of interest to biomedicine. The dissociation of carbonic and phosphoric acids and the solubility of calcium salts will be studied in isotonic saline. The systems chosen for study in the initial stages of the project are carbonic and phosphoric acid in isotonic saline as a simple matrix. Soluble proteins will be added to the buffer-salt systems to determine the existence and magnitude of a protein effect. The long term objectives are: (a) to recommend for standardization of ion sensors (H+, Na+, K+, Ca+2, F-, C1-), quantitative data on interferences, and new measurements procedures which will assist in removing errors (liquid junction potential) currently encountered in measurements with ion-selective electrode in the clinical laboratory, and (b) to furnish, for the first time, a quantitative measure of the effect of the electrolyte in saline media on the essential ionic processes which regulate acid-base chemistry in the human body under "real" conditions, to develop "metal ion buffers," based on the presence of chelating ligands (for example EDTA), as reference standards for use with ISEs in biological media.